In rheumatoid arthritis (RA), inflammatory cytokines play a pivotal role in triggering abnormal osteoclastogenesis leading to articular destruction. Recent studies have demonstrated enhanced levels of interleukin-9 (IL-9) in the serum and synovial fluid of patients with RA. In RA, strong correlation has been observed between tissue inflammation and IL-9 expression in synovial tissue. Therefore, we investigated whether IL-9 influences osteoclastogenesis in patients with RA. We conducted the study in active RA patients. For inducing osteoclast differentiation, mononuclear cells were stimulated with soluble receptor activator of NF-kB ligand (sRANKL) and macrophage-colony-stimulating factor (M-CSF) in the presence or absence of recombinant (r) IL-9. IL-9 stimulation significantly enhanced M-CSF/sRANKL-mediated osteoclast formation and function. Transcriptome analysis revealed differential gene expression induced with IL-9 stimulation in the process of osteoclast differentiation. IL-9 mainly modulates the expression of genes, which are involved in the metabolic pathway. Moreover, we observed that IL-9 modulates the expression of matrix metalloproteinases (MMPs), which are critical players in bone degradation. Our results indicate that IL-9 has the potential to influence the structural damage in the RA by promoting osteoclastogenesis and modulating the expression of MMPs. Thus, blocking IL-9 pathways might be an attractive immunotherapeutic target for preventing bone degradation in RA.

Introduction: The ongoing pandemic of COVID-19 has led to severe disruption of healthcare services worldwide. We conducted this study to assess the impact of COVID-19 pandemic on the management of Systemic Lupus Erythematosus (SLE) patients who were enrolled in the nation-wide inception cohort. Methods: A questionnaire was administered to the SLE patients enrolled in the inception cohort. Questions related to the effect on disease activity, preventive measures adopted against COVID-19, the incidence of COVID-19, hardships faced in getting access to health care professionals and availability of medicines, adherence, fear of COVID-19 and the potential benefits of being part of the registry. Results: A total of 1040 (90% females) patients completed the questionnaire. The mean age was 27.5 ± 19.1 years and the mean disease duration was 1.25 years. Twenty-Four (2.3%) patients had developed fever (>1 day) during this period, including one patient with additional symptoms of diarrhoea and anosmia, however, none of the patients developed COVID-19 infection. 262 patients (25.2%) reported financial difficulty during this period and patients reported an average excess expenditure of at least 2255.45 INR ($30) per month. 378 patients (36%) reported problems in getting their prescribed medicines due to lockdown. Of these, 167 (40%) patients needed to change their medication schedule due to this non-availability. Almost 54% of patients missed their scheduled follow up visits during the lockdown period and 37% of patients were unable to get their investigations done due to closure of laboratories and hospitals. 266 patients (25.5%) reported worsening of various symptoms of SLE during this period. Almost 61% patients felt confident that being associated with the inception cohort had helped them in managing their disease better during this period of lockdown as they received help in the form of timely and frequent telephonic consults, assistance in making the medicines available, and regular counselling resulting in abetment of their fears and anxieties. Conclusion: The current COVID-19 pandemic has made a huge impact on our SLE patients. Patients faced difficulty in the availability of medicines, missed the doses of medicines, had financial constraints, and spent more money on health during the pandemic.

A 32-year-old man presented to the rheumatology clinic with a several-year history of lower back pain and stiffness of the neck, shoulders, and hips. On examination, he had yellowish-brown tooth discoloration (Panel A) and restricted movements of the cervical spine, hips, and shoulders. Pelvic radiography showed osteosclerosis without sacroiliitis (Panel B). T scores for bone mineral density were +12.1 at the lumbar spine and +3.1 at the hip. Laboratory tests showed an alkaline phosphatase level of 479 IU per liter (reference range, 80 to 240) and a parathyroid hormone level of 103 pg per milliliter (reference range, 15 to 68), with normal levels of creatinine, calcium, and vitamin D. Since the patient lived in an area with high levels of fluoride in the groundwater, skeletal fluorosis was suspected. Radiography of both forearms showed interosseous membrane calcification (Panel C, arrowhead). The serum fluoride level was 0.05 ppm (reference value, <0.02 ppm), and the 24-hour urinary fluoride excretion was 7.5 ppm (reference value, <0.1 ppm), which confirmed the diagnosis. He was advised to defluorinate his drinking water and was treated with calcium, vitamin D, and nonsteroidal antiinflammatory drugs. Two years later, he reported a 50% reduction in pain and stiffness.

Urinary biomarkers may help in identification, treatment and assessment of response in patients with lupus nephritis (LN). Osteoprotegerin (OPG) is produced by the kidneys and lymphoid cells and may reflect renal disease activity better. The data on its utility are sparse. Fifty-eight patients with active LN (AN), 24 with active non-renal disease (ANR) and 39 with inactive disease (ID) were included. Median disease duration was 32 (1–204) months and median age was 27 (12–50) years. AN patients were followed up every three months for one year. Urine and serum samples were collected for OPG measurement by ELISA (pg/ml) and urinary values were normalised for creatinine excretion (pg/mg). Urine samples from 24 healthy individuals (HCs) and 20 patients each of rheumatoid arthritis (RA) and diabetic nephropathy (DM) served as controls. Variables were expressed as median (range). At baseline, normalised urinary OPG (uOPG) was significantly higher (p < 0.001) in AN (1229 (0–8577)) than ANR (236 (0–14713)), ID (463 (7–4253)), HCs (366 (120–2849)) and DM (350 (127–1577)) but it was not different from RA (1511 (122–8849)). uOPG correlated modestly with rSLEDAI (r = 0.4, p < 0.001) and SLEDAI (r = 0.31, p < 0.001) but not with serum OPG (sOPG). uOPG but not sOPG could differentiate between AN and ANR groups. In the longitudinal study, uOPG and sOPG decreased significantly with treatment at all follow-up visits but the trend of fall in sOPG was erratic. uOPG values at baseline, 3, 6, 9 and 12 months were 1229 (0–8577), 466 (3–4874), 104 (0–1598), 325 (0–4025) and 555 (6–6771) pg/mg, respectively. uOPG but not sOPG rose before conventional markers in three patients who had a relapse of LN. In two patients who developed chronic kidney disease, uOPG remained persistently high. For differentiating AN from ANR patients, uOPG performed the best on receiver operator characteristics analysis (AUC = 0.72) when compared with anti-dsDNA antibodies, C3, C4 and sOPG. uOPG is derived from kidneys and helps differentiate active SLE patients with and without LN. It shows modest correlation with disease activity and has a potential to predict poor response to therapy and relapse of LN.